title: Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens.
abstract: Establishing a cancer screening biomarker's intended performance requires "phase III" specimens obtained in asymptomatic individuals before clinical diagnosis rather than "phase II" specimens obtained from symptomatic individuals at diagnosis. We used specimens from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to evaluate ovarian cancer biomarkers previously assessed in phase II sets. Phase II specimens from 180 ovarian cancer cases and 660 benign disease or general population controls were assembled from four Early Detection Research Network or Ovarian Cancer Specialized Program of Research Excellence sites and used to rank 49 biomarkers. Thirty-five markers, including 6 additional markers from a fifth site, were then evaluated in PLCO proximate specimens from 118 women with ovarian cancer and 474 matched controls. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40. Except for transthyretin, these markers had similar or better sensitivity when moving to phase III specimens that had been drawn within 6 months of the clinical diagnosis. Performance of all markers declined in phase III specimens more remote than 6 months from diagnosis. Despite many promising new markers for ovarian cancer, CA125 remains the single-best biomarker in the phase II and phase III specimens tested in this study.
authors.affiliation: Brigham and Women's Hospital, Ob/Gyn, Division of Epidemiology, Boston, MA 02115, USA. dcramer@partners.org
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Anna E
authors.initials: AE
authors.lastname: Lokshin
authors.forename: Karen H
authors.initials: KH
authors.lastname: Lu
authors.forename: Martin W
authors.initials: MW
authors.lastname: McIntosh
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
authors.forename: Christos
authors.initials: C
authors.lastname: Patriotis
authors.forename: Paul F
authors.initials: PF
authors.lastname: Pinsky
authors.forename: Mark D
authors.initials: MD
authors.lastname: Thornquist
authors.forename: Nathalie
authors.initials: N
authors.lastname: Scholler
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Skates
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sluss
authors.forename: Sudhir
authors.initials: S
authors.lastname: Srivastava
authors.forename: David C
authors.initials: DC
authors.lastname: Ward
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Claire S
authors.initials: CS
authors.lastname: Zhu
authors.forename: Nicole
authors.initials: N
authors.lastname: Urban
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D018070:Biological Specimen Banks; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor